Migration inhibitory factor (MIF) and Type II interferon were released into the circulation of tuberculin hypersensitive mice after intravenous challenge with old tuberculin (OT). The mice could be sensitized intravenously not only with living BCG but also with BCG cell walls in Drakeol-Tween and with a mixture of PPD and P3 (a mycolic acid ester of trehalose). A close correlation existed between the conditions of sensitization that resulted in maximum release of lymphokines (MIF and Type II interferon) and those conditions that caused protection against aerosol challenge with a virulent strain of Mycobacterium tuberculosis. With the use of neonatal thymectomy, anti-O sera, anti-B-cell sera, and cell reconstitution studies, results indicated that both B and T cells seem involved in the production and release of MIF into the circulation of mice with delayed hypersensitivity after challenge with specific antigen. Specific suppression of delayed hypersensitivity to purified proteins was associated with the onset of antibody production. The adoptive transfer of this specific suppression to sensitized animals was effectively carried out with splenic cells, and not with peritoneal exudate (PE) cells, from donors in a state of suppression. Thus, suppressin of delayed hypersensitivity seems not to be dependent on a T- cell resident in the peritoneal exudate.